Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Human herpes virus (HHV) specific immune effector (IE) cells for prevention and treatment of HHV-related diseases
Acronym
Study hypothesis
Human herpes viruses, including Epstein-Barr virus (EBV), cytomegalovirus (CMV) and HHV type 6 (HHV6) are common pathogens in humans. In healthy individuals, HHV infection is often self-resolved. However, in immune compromised individuals such as transplant patients, or young and elderly individuals, HHV-related diseases can be lethal. The development of an effective immune response is the best solution to treating HHV diseases. We hypothesise that HHV-specific immune effector cells can be used to prevent or cure HHV infections including EBV-associated lymphomas. Such immune effector cells can come from the recipients own blood, or their allogeneic transplant donors' blood. HHV-specific immune effector (IE) cells will be generated in culture and infused into patients. The safety of this approach, and virus titre and HHV-associated diseases will be closely monitored. The study will determine if HHV-specific IE cells can be used to prevent HHV infections and treat HHV-related diseases.
Ethics approval
Institutional Review Board of Shanghai Dao-Pei Hospital, Institute of Hematology, Fu Dan University gave approval on the 10/05/07 (ref: SHDP-2007-0510)
Study design
Phase I/II trial, non-blind, single-site, single-group (compared with historical database) study
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Human herpes virus (HHV) infections
Intervention
The trial enrols paediatric and adult patients with potential of developing HHV-related diseases to receive immune cell infusions. The pre-emptive/preventive arm of treatment is a Phase I/II trial, non-blind, single-site, single-group (compared with historical database) study, and the subjects will be followed up for one year after treatment. Each subject will receive four infusions of HHV-specific immune effector cells after haematopoietic stem cell transplantation, with seven follow-ups: one week after the last infusion, one month thereafter for three months, and every three months thereafter until the end of the trial.
The previous sponsor for this trial (up to 02/07/2013) was:
Vectorite Biomedica Inc.
WR-09, 17th Fl
3 Yuan Qu Street
Taipei
001
Taiwan
Intervention type
Drug
Phase
Phase I/II
Drug names
EBV-specific immune effector cells
Primary outcome measure
1. Patients' immediate clinical response after IE cell infusion, i.e. body temperature and symptoms related to GvHD
2. Virus titre or DNA copy in blood or tissue biopsy
3. HHV-associated diseases such as EBV-associated post-transplant lymphoproliferative disorder (PTLD)
Outcomes are measured at 24 hours, day 2, day 3, day 4, day 5, day 6, day 7, week 2, week 4, month 2, month 3, month 6 and year 1.
Secondary outcome measures
1. Production: IE cell preparation success rate - the minimal IE cell number can be generated per subject
2. Efficacy:
2.1. Tracking HHV titre or copy number
2.2. HHV IE cell function analysis in vitro and its correlation with in vivo effect
2.3. Effect on PTLD - for subjects with EBV-PTLD
2.4. Effect on mononucleosis - body temperature and HHV titre will be monitored
2.5. Survival rate and the time required to recover completely from HHV diseases
3. Prevention: determine the time and frequency of HHV disease incidence in subjects after the first IE cell infusion, in comparison to historically-documented uninfused subjects
4. Safety:
4.1. Adverse effect documentation
4.2. National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or above respose
4.3. Changes in biochemical parameters
4.4. Complete blood count (CBC)
4.5. SGPT (aspartate aminotransferase [AST]), SGOT (alanine aminotransferase [ALT]), total bilirubin, gamma-glutamyl transferase (g-GT)
4.6. Creatinine, blood urea nitrogen (BUN), uric acid
4.7. Physical response
4.8. Life sign changes
4.9. Blood pressure
4.10. Pulse
4.11. Temperature
Outcomes are measured at 24 hours, day 2, day 3, day 4, day 5, day 6, day 7, week 2, week 4, month 2, month 3, month 6 and year 1.
Overall trial start date
25/06/2007
Overall trial end date
25/06/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. The participants should meet at least one of the following conditions:
1.1. Bone marrow transplant (BMT) or solid organ transplant (SOT) patient:
1.1.1. High-risk subject of lymphoproliferative disease: e.g. donor is HHV sero-positive (human herpes virus viral capsid antigen immunoglobulin G positive [HHV VCA IgG+]) and recipient is HHV sero-negative (HHV VCA IgG-) at time of transplantation
1.1.2. The subject has history of human herpes virus-associated lymphoproliferative disorder (HHV-LPD) or HHV-related malignancy
1.1.3. The subject develops HHV diseases and not considered suitable for conventional treatment
1.1.4. The subject shows human herpes virus deoxyribonucleic acid (HHV DNA) greater than or equal to 1000 genome copies/µg in the peripheral blood (with or without LPD) in two consecutive samplings (24 hours apart)
1.1.5. HHV reactivation
1.2. HHV-infected subjects:
1.2.1. Subject develops HHV LPD and not suitable for conventional treatment
1.2.2. The subject shows HHV DNA greater than or equal to 1000 genome copies/µg in the peripheral blood (with or without LPD) in two consecutive samplings (24 hours apart)
1.2.3. HHV reactivation
2. Aged less than or equal to 65 years, either sex
3. Subject blood:
3.1. White blood cell count (WBC) greater than or equal to 3500/µl
3.2. Blood lymphocytes greater than or equal to 750/µl
4. Liver and kidney function:
4.1. Creatinine less than or equal to 1.25 time of upper limit
4.2. Bilirubin less than or equal to 1.5 time of upper limit
4.3. Serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 3 time of upper limit
4.4. Serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 time of upper limit
5. Donor condition:
5.1. No chemo- or radiation-therapy within 4 weeks of blood collection; no steroid use within 1 week of blood collection
5.2. WBC greater than or equal to 3500/µl
5.3. Lymphocytes greater than or equal to 750/µl
6. Signed informed consent
Participant type
Patient
Age group
Other
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. Donor or recipient shows hepatitis C virus (HCV), human immunodeficiency virus (HIV) or tuberculosis (TB) positive
2. Recipient develops grade IV graft-versus-host disease (GvHD)
3. Recipient is albumin-intolerant
4. Recipient life expectancy less than 8 weeks
5. Recipient received alternative cell therapy within 30 days
6. Recipient is pregnant
Recruitment start date
25/06/2007
Recruitment end date
25/06/2015
Locations
Countries of recruitment
China
Trial participating centre
Shanghai Dap-Pei Hospital
Shanghai
201100
China
Sponsor information
Organisation
America Yuva Biomed Inc. (China)
Sponsor details
B105
Zhongguancun Biomedical Garden
Kaituo rd.no.5
Haidian District
Beijing
100085
China
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Current sources of funding as of 02/07/13:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
America Yuva Biomed Inc. (China)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Previous sources of funding:
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Vectorite Biomedica Inc. (Taiwan)
Alternative name(s)
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Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list